PPARγ non-agonist ligand:the structure optimization based on PPARγ partial agonist
10.16438/j.0513-4870.2017-0318
- VernacularTitle:PPARγ非激动配体:基于PPARγ部分激动剂的结构优化
- Author:
Yi ZHENG
1
;
Yi HUAN
2
;
Shou-xin LIU
1
;
Li-jing ZHANG
2
;
Yue WANG
2
;
Xing WANG
2
;
Zhi-qiang FENG
2
;
Zhu-fang SHEN
2
Author Information
1. Hebei University of Science and Technology, Shijiazhuang 050018, China
2. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
insulin sensitizer;
PPARγ non-agonist ligand;
PPARγ partial agonist;
type 2 diabetes
- From:
Acta Pharmaceutica Sinica
2017;52(9):1424-1431
- CountryChina
- Language:Chinese
-
Abstract:
Recent studies indicate that insulin-sensitizing activity of TZDs occurs through the inhibition of PPARγ Ser273 phosphorylation mediated by cyclin-dependent kinase 5(Cdk5), which is resulted from the binding activity for PPARγ. While, the side effects of TZDs may be related to the agonistic potency for PPARγ. In this article, 15 target compounds were designed and synthesized based on the structure of PPAR γ partial agonist INT131, with the aim of maintaining the insulin-sensitizing activity and reducing the side effects of INT131. The structures of these compounds were confirmed by 1H NMR and ESI-MS, and their binding activities and agonistic potencies for PPARγ were measured. The binding activity of compound 15 is 88.47% of rosiglitazone, which is similar to INT131 (98.55%), but the agonistic potency of compound 15 is 1.41% of rosiglitazone, obviously lower than INT131 (15.18%).
